ATP1A3
Identifiers
AliasesATP1A3, AHC2, DYT12, RDP, CAPOS, ATPase Na+/K+ transporting subunit alpha 3, ATP1A1, DEE99
External IDsOMIM: 182350 MGI: 88107 HomoloGene: 113729 GeneCards: ATP1A3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001256213
NM_001256214
NM_152296

NM_001290469
NM_144921
NM_001374627

RefSeq (protein)

NP_001243142
NP_001243143
NP_689509

NP_001277398
NP_001361556

Location (UCSC)Chr 19: 41.97 – 42 MbChr 7: 24.68 – 24.71 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Sodium/potassium-transporting ATPase subunit alpha-3 is an enzyme that in humans is encoded by the ATP1A3 gene.[5][6]

Function

The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of Na+/K+-ATPases. Na+/K+-ATPase is an integral membrane protein responsible for establishing and maintaining the electrochemical gradients of Na and K ions across the plasma membrane. These gradients are essential for osmoregulation, for sodium-coupled transport of a variety of organic and inorganic molecules, and for electrical excitability of nerve and muscle. This enzyme is composed of two subunits, a large catalytic subunit (alpha) and a smaller glycoprotein subunit (beta). The catalytic subunit of Na+/K+-ATPase is encoded by multiple genes. This gene encodes an alpha 3 subunit.[6] ATP1A3 is expressed early in human development, likely underlying pathophysiology related to several ATP1A3 related diseases.[7]

Clinical significance

Disease causing variants of the ATP1A3 gene are known to cause a variety of movement disorders and epilepsies.[8] The known associations include a variety of syndromes, in approximate order of presentation:

  1. Malformation of Cortex Development, including polymicrogyria[7]
  2. Developmental and epileptic encephalopathy
  3. Alternating hemiplegia of childhood (AHC)
  4. Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss (CAPOS/CAOS syndrome)
  5. Very early-onset schizophrenia[9]
  6. Rapid onset dystonia-parkinsonism (RDP, also known as DYT12)
  7. Fever induced paroxysmal weakness and encephalopathy (FIPWE)
  8. Recurrent episodes of cerebellar ataxia (RECA)

In mice, mutations in this gene are associated with epilepsy. By manipulating this gene in the offspring of such mice, epilepsy can be avoided.[10]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000105409 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040907 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Brashear A, Dobyns WB, de Carvalho Aguiar P, Borg M, Frijns CJ, Gollamudi S, Green A, Guimaraes J, Haake BC, Klein C, Linazasoro G, Münchau A, Raymond D, Riley D, Saunders-Pullman R, Tijssen MA, Webb D, Zaremba J, Bressman SB, Ozelius LJ (Mar 2007). "The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene". Brain. 130 (Pt 3): 828–35. doi:10.1093/brain/awl340. PMID 17282997.
  6. ^ a b "Entrez Gene: ATP1A3 ATPase, Na+/K+ transporting, alpha 3 polypeptide".
  7. ^ a b Smith RS, Florio M, Akula SK, Neil JE, Wang Y, Hill RS, et al. (2021-06-22). "Early role for a Na + ,K + -ATPase ( ATP1A3 ) in brain development". Proceedings of the National Academy of Sciences. 118 (25): e2023333118. doi:10.1073/pnas.2023333118. PMC 8237684. PMID 34161264.
  8. ^ Papandreou A, Danti FR, Spaull R, Leuzzi V, Mctague A, Kurian MA (February 2020). "The expanding spectrum of movement disorders in genetic epilepsies". Developmental Medicine and Child Neurology. 62 (2): 178–191. doi:10.1111/dmcn.14407. PMID 31784983. S2CID 208498567.
  9. ^ Smedemark-Margulies N, Brownstein CA, Vargas S, Tembulkar SK, Towne MC, Shi J, Gonzalez-Cuevas E, Liu KX, Bilguvar K, Kleiman RJ, Han MJ, Torres A, Berry GT, Yu TW, Beggs AH, Agrawal PB, Gonzalez-Heydrich J (September 2016). "A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia". Cold Spring Harbor Molecular Case Studies. 2 (5): a001008. doi:10.1101/mcs.a001008. PMC 5002930. PMID 27626066.
  10. ^ Clapcote SJ, Duffy S, Xie G, Kirshenbaum G, Bechard AR, Rodacker Schack V, Petersen J, Sinai L, Saab BJ, Lerch JP, Minassian BA, Ackerley CA, Sled JG, Cortez MA, Henderson JT, Vilsen B, Roder JC (August 2009). "Mutation I810N in the alpha3 isoform of Na+,K+-ATPase causes impairments in the sodium pump and hyperexcitability in the CNS". Proc. Natl. Acad. Sci. U.S.A. 106 (33): 14085–90. Bibcode:2009PNAS..10614085C. doi:10.1073/pnas.0904817106. PMC 2729024. PMID 19666602.

Further reading